1. Field of the Invention
The present invention is directed to pharmaceutical compositions comprising as active ingredients one or more 3- and 4-substituted 2(5H)-furanone compounds, and methods for administering such compositions to mammals, including humans, for the purpose of inhibiting bone loss.
2. Brief Description of the Prior Art
Osteoporosis is a disease which manifests itself in a decrease of bone density throughout the body. The descreased bone density is due to loss of calcium containing bone mineral and also due to loss of bone matrix (collagen). The disease of osteoporosis usually afflicts elderly patients, more frequently post menopausal women, although beyond the age of 80 the frequency of the disease is about the same in men as in women. The cause of osteoporosis is not well understood, nevertheless it is believed that bone is continuously formed and resorbed during the life of a mammal, including human, and that in persons suffering from osteoporosis the rate of bone resorption is faster than the rate of bone formation, resulting in a net loss of bone density. Thus, osteoporosis is a disease where the balance between bone production and resorption, especially the balance of deposit and resorption of calcium in the bone, is disturbed.
The present methods for treating osteoporosis include physical therapy, administration of anabolic agents, drugs containing phosphorous, vitamin D, calcium salts, fluoride salts calcitonin, and of the antibiotic mithramycin. In post-menopausal women estrogen replacement therapy is also employed to prevent or lessen bone loss.
Among the foregoing, mithramycin is believed to decrease the rate of bone desorption, and thus modify the balance between bone production and resoption. The prior art which is believed to be closest to the present invention is U.S. Pat. No. 4,916,241 describing certain 5-hydroxy-2(5H)-furanone derivatives which are substituted in the 4 position with a substituted phenyl-methyl, substituted phenylhydroxymethyl, substituted phenyl alkyl, or with substituted phenyl-hydroxyalkyl groups, and which modify the balance between bone production and bone resorption in a host animal, including man.
As further background to the present invention, it is noted that several types of 4-substituted 2(5H)-furanone derivatives, especially 4-substituted 5-hydroxy-2(5H)-furanone derivatives, and certain 3 substituted 2(5H)-furanones as well, have been discovered and disclosed in the prior art to be anti-inflammatory, calcium channel blocking and/or antiproliferative agents. However, to the best knowledge of the present inventor the only disclosure of 4-substituted-5-hydroxy-2(5H)-furanone compounds as agents for modifying the balance between bone production and bone resorption is in the above-noted U.S. Pat. No. 4,916,241 reference.
Unfortunately, none of the known methods for treatment of osteoporosis, or more broadly speaking, methods for favorably modifying the balance between bone production and resorption, are entirely satisfactory. Therefore, the search continues in the art for better and/or additional agents for inhibiting bone loss. The present invention represents an important discovery and advance in the art in this regard.